Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brotizolam is a new thienotriazolodiazepine derivative with a pharmacological profile similar to that of benzodiazepines. It is indicated for use as an hypnotic in the management of insomnia, although it also has anticonvulsant, antianxiety and muscle relaxant properties in animals. In clinical trials brotizolam 0.125 to 0.5mg improved sleep in insomniacs similarly to nitrazepam 2.5 and 5mg, flunitrazepam 2mg and triazolam 0.25mg, whilst brotizolam 0.5mg was shown to be superior to flurazepam 30mg in some studies. Brotizolam is an effective hypnotic for hospital patients awaiting surgery, in whom it also reduces anxiety. Brotizolam has an elimination half-life of about 5 hours, which is 'intermediate' compared with the shorter-acting hypnotic, triazolam, and longer-acting benzodiazepines. Consequently, it is able to induce sleep without producing early morning rebound insomnia, and can also maintain sleep throughout the night. Brotizolam at dosages below 0.5mg at night usually produced minimal morning drowsiness; no residual impairment of psychomotor performance occurs following dosages within the recommended range of 0.125 to 0.25 mg/kg. No serious side effects have been reported to date and the most frequently observed adverse experiences are drowsiness, headache and dizziness. Mild rebound insomnia may occur in some patients when treatment is stopped. Thus, brotizolam is a useful hypnotic which can be used in patients who have difficulty in falling asleep and also in patients who are troubled by night-time awakenings. Used in the recommended dosage it may be particularly useful for patients in whom daytime impairment of performance is unacceptable.
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PMID:Brotizolam. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an hypnotic. 328 19

Sixty-three outpatients with chronic insomnia were treated for 3 weeks under double-blind conditions with either brotizolam (n = 29) at a dose of 0.25 mg or 0.5 mg or placebo (n = 34). A 3-day placebo period preceded and followed the double-blind treatment phase. Brotizolam consistently produced significantly more sleep improvement than placebo but also more adverse effects. In those patients switched abruptly from brotizolam to placebo, rebound insomnia was observed, being most marked at the first post-brotizolam placebo night.
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PMID:Brotizolam, a triazolothienodiazepine, in insomnia. 352 13

A double-blind, crossover study was carried out in general practice on the hypnotic activity of 0.25 mg brotizolam in patients aged between 18 and 70 years complaining of insomnia (11 men, 28 women). Patients reported that they slept better, that they awoke less frequently and that they slept longer with brotizolam than with placebo. Overall the patients preferred brotizolam to placebo, and subjective assessments of well-being after brotizolam did not differ from those after placebo. Brotizolam was well tolerated and there were no incidents of note.
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PMID:Hypnotic activity of brotizolam: a study in general practice. 636 1

Brotizolam 0.25 mg was evaluated in a sleep laboratory study of 10 normal subjects. The study covered 10 consecutive nights and included 4 placebo-baseline nights, 3 nights on the drug and 3 placebo-withdrawal nights, which permitted assessment of initial drug effects, side effects and withdrawal phenomena, such as rebound insomnia. There was a significant increase in total sleep time with drug administration; the improvement in sleep occurred primarily in the first third of the night following the onset of sleep. During the day after nightly drug administration, the presence of rebound anxiety was suggested by an increase in reports of anxiety/tension as compared to baseline. Following drug withdrawal there was a significant increase in total wake time above baseline level, to 40% above baseline on the first and third nights of withdrawal.
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PMID:Brotizolam: a sleep laboratory evaluation. 661 24

Effects of ingestion of brotizolam (0.25 and 0.50 mg) over 1-3 days on polysomnographic measures of sleep were assessed in patients complaining of insomnia. Brotizolam reduced latency to sleep, number of awakenings and wake during sleep, and increased total sleep time. It also increased stage 2 sleep and decreased slow wave and rapid eye movement sleep. Increasing the dose from 0.25 to 0.50 mg increased hypnotic efficacy, and there was a more consistent and reliable effect. Discontinuation of brotizolam had minimal effects on sleep compared with placebo over the 3 nights after acute administration. No side-effects or disruption of daytime function was found using questionnaires and objective tests of performance.
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PMID:Effects of acute administration of brotizolam in subjects with disturbed sleep. 666 83

Effects of 0.5 mg brotizolam on the sleep of chronic insomniacs were assessed electroencephalographically and subjectively over 14 days. Brotizolam (0.5 mg) increased total sleep time, decreased drowsy (stage 1) sleep and increased stage 2 sleep. At this dose it also decreased slow wave and rapid eye movement sleep. On withdrawal there was evidence of insomnia in some subjects during the first night. The drug was well tolerated. Further studies are indicated with lower doses of the drug.
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PMID:Effects of brotizolam on the sleep of chronic insomniacs. 666 84

Brotizolam (0.25 mg) was compared with placebo, and in a separate study, with nitrazepam (5.0 mg) in patients being treated for insomnia in general practice. Brotizolam (0.25 mg) and nitrazepam (5.0 mg) were equally effective and there was no evidence of residual effects the next day with either drug.
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PMID:Studies in general practice with brotizolam. 666 86

The present study was performed to see if first-generation histamine H1-antagonists are useful sedative-hypnotic drugs. Increases in electroencephalogram (EEG) power spectra of the delta band (0-4 Hz) at the frontal cortex and theta band (4-8 Hz) at the hippocampus in rats were used as an indexes of sleep. The H1-antagonists used in this study resulted in a decrease in sleep latency and an increase in sleep duration (slow wave sleep). The rate of REM (rapid eye movement) sleep during slow wave sleep was decreased by H1-antagonists and brotizolam. The order of potency of H1-antagonists for the reduction in sleep latency (from greatest to least) was promethazine>chlorpheniramine>diphenhydramine and pyrilamine, and that for the increase in sleep duration was chlorpheniramine>promethazine>diphenhydramine and pyrilamine. Brotizolam was more potent than these H1-antagonists, with 14-18-fold and 4-14-fold greater effects on sleep latency and duration, respectively. These results clearly show that H1-antagonists are effective in mild to moderate insomnia as sedative-hypnotic drugs.
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PMID:Slow wave sleep-inducing effects of first generation H1-antagonists. 1054 59

Triazolam reportedly causes phase advances in hamster wheel-running rhythm after injection during subjective daytime. However, it is unclear whether benzodiazepine affects the PER: gene expression accompanying a behavioural phase shift. Brotizolam (0.5 - 10 mg kg(-1)) induced large phase advances in hamster rhythm when injected during mid-subjective daytime (circadian time 6 or 9), but not at circadian time 0, 3 or 15. Brotizolam (5 mg kg(-1)) significantly reduced the expression of PER:1 and PER:2 in the suprachiasmatic nucleus 1 and 2 h after injection at circadian time 6, and slightly reduced them at circadian time 20. Injection of 8-OH-DPAT (5 mg kg(-1)) at subjective daytime induced similar phase advances with a reduction of PER:1 and PER:2 expression. Co-administration of brotizolam with 8-OH DPAT failed to potentiate the 8-OH DPAT-induced phase advances and reduced PER: expression. Both phase advance and rapid induction of PER:1 and PER:2 in the suprachiasmatic nucleus after light exposure (5 lux, 15 min) at circadian time 20 was strongly attenuated by co-treatment with brotizolam 5 mg kg(-1). The present results strongly suggest that reduction of PER:1 and/or PER:2 expression during subjective daytime by brotizolam may be an important step in causing a behavioural phase advance. The co-administration experiment suggests that common mechanism(s) are involved in brotizolam- or 8-OH DPAT-induced phase advances and the reduction of PER: gene expression. These results suggest that brotizolam is not only a good drug for insomnia but also a drug capable of facilitating re-entrainment like melatonin.
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PMID:Inhibitory action of brotizolam on circadian and light-induced per1 and per2 expression in the hamster suprachiasmatic nucleus. 1113 54